Baicalein Inhibits Proliferation, Migration, and Invasion of Mesothelioma Cells Through the p53–FOXM1 Signaling Axis

Xin-Yi Zheng,1,2,* Chao Guo,2,* Jie Peng,3,* Ping-Xiang Tang,1,2 Ze Xia,2 Wen-Fei Xu,2 Xu-Hui Li1,2 1College of Fisheries and Life Science, Shanghai Ocean University, Shanghai, People’s Republic of China; 2Zhejiang Key Laboratory of Multiomics and Molecular Enzymology, Yangtze Delta Region Institute of Tsinghua University, Zhejiang, Jiaxing, Zhejiang, 314006, People’s Republic of China; 3Women’s Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xu-Hui Li, Zhejiang Key Laboratory of Multiomics and Molecular Enzymology, Yangtze Delta Region Institute of Tsinghua University, Zhejiang, Jiaxing, Zhejiang, 314006, People’s Republic of China, Email [email protected] Wen-Fei Xu, Zhejiang Key Laboratory of Multiomics and Molecular Enzymology, Yangtze Delta Region Institute of Tsinghua University, Zhejiang, Jiaxing, Zhejiang, 314006, People’s Republic of China, Email [email protected]: Baicalein, a natural flavonoid derived from the root of Scutellaria baicalensis, has demonstrated antitumor efficacy in several cancers. However, its effects on human mesothelioma remain largely unclear. This study evaluates the antitumor roles and mechanisms of baicalein in mesothelioma cell lines.Materials and Methods: Effects of baicalein on mesothelioma cells phenotypic changes were investigated by measuring cell proliferation, apoptosis, migration, invasion, and cell-cycle alterations. Bioinformatic methods were applied to predict the mechanisms by which baicalien mediated its antitumor roles in mesothelioma. Crucial signaling molecules among p53-FOXM1 signaling axis, including p53, FOXM1 and cyclin B1, were evaluated by immunoblotting in mesothelioma cells.Results: Treatment with baicalein significantly inhibited mesothelioma cell viability in a dose-dependent manner, with 48 h IC50 values of 48.9 μM for MESO257 and 53.2 μM for MESO924. Baicalein also markedly reduced cell migration and invasion, while inducing apoptosis in both cell lines. Mechanistically, baicalein suppressed the p53-FOXM1 signaling axis, decreasing FOXM1 and Cyclin B1 while increasing p53 expression. Furthermore, FOXM1 overexpression attenuated the antiproliferative, anti-migratory, anti-invasive and proapoptotic effects of baicalein.Conclusion: Baicalein suppresses mesothelioma cell growth and invasion in vitro through modulation of the p53–FOXM1 signaling axis. These findings support its potential as a lead compound for further preclinical evaluation in mesothelioma.Keywords: Baicalein, traditional Chinese medicine, antitumor activity, mesothelioma, p53, FOXM1